Development and testing of an alternative responder definition for EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)

Objectives Dryness, fatigue and joint/muscle pain are typically assessed in Sjogren's trials using European Alliance of Associations for Rheumatology Sjogren's Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of <5 and a Minimal Clinically Important Improvement (MCII)/responder definition (RD) of >= 1 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials. Methods Anchor-based and distribution-based methods were used to derive RD thresholds in blinded phase IIb trial data (N=190) and confirm these in blinded data pooled from three early phase II trials (N=126). The populations consisted of individuals with moderate-to-severe systemic primary Sjogren's. Anchors were prioritised by ESSPRI correlations and used in similar conditions. Triangulated estimates were discussed with experts (N=3). The revised RD was compared with the original using unblinded data to assess placebo and treatment responder rates. Results Patients were predominantly female (>90%), white (90%), with mean age of 50 years. Receiver operating characteristic estimates supported an MCII threshold of 1.5-1.6 in the phase II data, whereas correlation-weighted mean change estimates supported a low/minimal symptom severity threshold of >= 2. A low/minimal symptom severity of <= 3 showed the greatest sensitivity/specificity balance. Analyses in the pooled data supported these thresholds (MCII: 1.5-2.1; low/minimal symptom severity: 2.7-3.7). Unblinded analyses confirmed the revised RD reduced placebo rates. Conclusions Completing a trial with an improvement of >= 1.5 points compared with baseline and an ESSPRI score of <= 3 points is a relevant RD for moderate-to-severe systemic Sjogren's and reduces placebo rates.